Drug Groups

approved

Description

Imatinib is a drug used to treat certain types of cancer. It is currently marketed by Novartis as Gleevec (USA) or Glivec (Europe/Australia) as its mesylate salt, imatinib mesilate (INN). It is occasionally referred to as CGP57148B or STI571 (especially in older publications). It is used in treating chronic myelogenous leukemia (CML), gastrointestinal stromal tumors (GISTs) and a number of other malignancies.

It is the first member of a new class of agents that act by inhibiting particular tyrosine kinase enzymes, instead of non-specifically inhibiting rapidly dividing cells.

Indication

For the treatment Philadelphia chromosome positive chronic myeloid leukemia (CML) and malignant gastrointestinal stromal tumors (GIST).

Pharmacology

Imatinib is an antineoplastic agent used to treat chronic myelogenous leukemia. Imatinib is a 2-phenylaminopyrimidine derivative that functions as a specific inhibitor of a number of tyrosine kinase enzymes. In chronic myelogenous leukemia, the Philadelphia chromosome leads to a fusion protein of Abl with Bcr (breakpoint cluster region), termed Bcr-Abl. As this is now a continuously active tyrosine kinase, Imatinib is used to decrease Bcr-Abl activity.

Toxicity

Side effects include nausea, vomiting, diarrhea, loss of appetite, dry skin, hair loss, swelling (especially in the legs or around the eyes) and muscle cramps

Affected Organisms

Biotransformation

Primarily hepatic via CYP3A4. Other cytochrome P450 enzymes, such as CYP1A2, CYP2D6, CYP2C9, and CYP2C19, play a minor role in its metabolism. The main circulating active metabolite in humans is the N-demethylated piperazine derivative, formed predominantly by CYP3A4.

Absorption

Imatinib is well absorbed with mean absolute bioavailability is 98% with maximum levels achieved within 2-4 hours of dosing

Half Life

18 hours for Imatinib, 40 hours for its major active metabolite, the N-desmethyl derivative

Protein Binding

Very high (95%)

Elimination

Imatinib elimination is predominately in the feces, mostly as metabolites.

Clearance

* 8 L/h [50-year-old CML and GIST patient weighing 50 kg]
* 14 L/h [50-year-old CML and GIST patient weighing 100 kg]

References

External Links